Characterization of the human class Mu glutathione S-transferase gene cluster and the GSTM1 deletion.
A partial physical map has been constructed of the human class Mu glutathione S-transferase genes on chromosome 1p13.3. The glutathione S-transferase genes in this cluster are spaced about 20 kilobase pairs (kb) apart, and arranged as 5'-GSTM4-GSTM2-GSTM1-GSTM5-3'. This map has been used to localize the end points of the polymorphic GSTM1 deletion. The left repeated region is 5 kb downstream from the 3'-end of the GSTM2 gene and 5 kb upstream from the beginning of the GSTM1 gene; the right repeated region is 5 kb downstream from the 3'-end of the GSTM1 and 10 kb upstream from the 5'-end of the GSTM5 gene. The GSTM1-0 deletion produces a novel 7.4-kb HindIII fragment with the loss of 10.3- and 11.4-kb HindIII fragments. The same novel fragment was seen in 13 unrelated individuals (20 null alleles), suggesting that most GSTM1-0 deletions involve recombinations between the same two regions. We have cloned and sequenced the deletion junction that is produced at the GSTM1-null locus; the 5'- and 3'-flanking regions are more than 99% identical to each other and to the deletion junction sequence over 2.3 kb. Because of the high sequence identity between the left repeat, right repeat, and deletion junction regions, the crossing over cannot be localized within the 2.3-kb region. The 2.3-kb repeated region contains a reverse class IV Alu repetitive element near one end of the repeat.
Xu
S
S
Department of Biochemistry, University of Virginia, Charlottesville, Virginia 22908, USA.
Wang
Y
Y
Roe
B
B
Pearson
W R
WR
D001483:Base Sequence; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D004247:DNA; D017353:Gene Deletion; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D011993:Recombinant Fusion Proteins; D004247:DNA; D005982:Glutathione Transferase